Our laboratory recently reported that the polarity complex (atypical PKC-Par3-Par6), an evolutionarily conserved signaling pathway is deeply downregulated under inflammatory TNF signaling. It is also downregulated in a mouse model of colitis as well as in ulcerative colitis and Crohn's disease patients. Because Inflammatory Bowel Disease represents a substantial problem for human health, I would like to further analyze the downstream consequences of aPKC downregulation. Our published and preliminary data show that the polarity complex exerts antagonistic control on the activation of non-muscle Myosin IIA, a broadly accepted effector of inflammatory signaling in epithelial cells. Other laboratories have shown the involvement of nmMyosin II in tight junction maintenance and downstream of inflammatory signaling, but we are the first to postulate specifically one of the isoforms nmMyoIIA as the main molecular mechanism controlling epithelial barrier. Accordingly, here I put forth the hypothesis that: Inflammation-dependent downregulation of the polarity complex aPKC is a novel signaling mechanism that synergistically upregulates the apical expression of nmMyosinIIA abrogating direct phosphorylation of the heavy chains. This project is devoted to analyze the effects and the molecular mechanisms by which aPKC-Par3-Par6 antagonizes MLCK- mediated nmMyosin II activation.